Human lymphoid leukemias are phenotypically heterogenous diseases, the subtypes of which appear to represent clonal cells that are arrested at specific stages of lymphoid ontogeny. Individual phenotypes of leukemia are defined by cell surface antigens, programmed gene rearrangements and selected enzyme markers. One of these markers, terminal deoxynucleotidyl transferase, is expressed only in normal prelymphocytes and their neoplastic counterparts. It has been proposed that terminal transferase activity is responsible for addition of N regions (extra random nucleotides) to DNA during rearrangement of immunoglobulin heavy chain genes or T cell receptor beta genes. Recently, cDNAs coding for human terminal transferase have been cloned and used to isolate the gene coding for this enzyme. The terminal transferase gene is large (-50 kb) and appears to exist in low copy number in normal tissues. The goal of this proposal is to determine structure of the terminal transferase gen in normal and neoplastic tissues. Preliminary data suggest that the structure of the gene is altered in various tissues. This study will assess tissue specific, individual and leukemia-associated polymorphisms in the gene and its regulatory region, using Southern genomic blotting and in situ hybridization techniques. The expression of terminal transferase mRNA, antigen and activity will be assessed in selected cells and correlated with the structural data derived from studies of the gene. Integration of these data will yield a comprehensive picture of structure/ function correlates of this gene in normal and leukemic cells.